Twenty years ago, W. Dalton Dietrich and his colleagues had a problem: the rats in their laboratory experienced the same kind of stroke but had dramatically different outcomes.
”We were perplexed,” Dietrich says.
To try to figure out what was going on, they started measuring the temperature of the rats’ brains. The results were shocking.
Rats whose brains were just a few degrees cooler than normal fared far better than others. Outcomes for those whose brains were a few degrees warmer than normal were, in Dietrich’s words, “really, really, really bad.”
That discovery inspired new interest in an old idea that had lost favor: using hypothermia to help patients who have suffered grave harm to the heart, brain or spinal cord. Now research is moving out of the laboratory and into the clinic. Some studies have shown no benefit from inducing hypothermia, but others have shown great promise.
Doctors are using a wide range of techniques for cooling — from simple ice packs to high-tech machines that run cold fluid through the veins. Specific treatments vary, but patients are typically cooled until their body temperature is in the low 90s (98.6 is normal), and kept that way for 12 to 48 hours. Treatment must be started early — usually within hours of the injury or cardiovascular event.
Last year, following the publication of two major studies, the American Heart Association recommended inducing hypothermia in some patients after cardiac arrest. Doctors at Jackson Memorial Hospital plan to adopt the recommendations in the coming months, said Dr. Kathy Schrank, who runs the hospital’s emergency department.
In other studies, doctors are cooling oxygen-deprived newborns as well as adults who have suffered strokes, heart attacks and traumatic brain injuries.
At the Miami Project to Cure Paralysis, where Dietrich is now scientific director, researchers are trying to understand exactly how temperature variations affect cell behavior. And Dr. Barth Green, the Miami Project’s co-founder, is inducing hypothermia in some of the most gravely injured spinal cord patients in the minutes or hours after they arrive at the trauma center.
”It’s a wonderful opportunity for us, for the first time ever, to protect the spinal cord after injury,” Green says.
Manny Gomez, a policeman who fell from his horse in January, was the first South Florida spinal cord trauma patient to be treated with hypothermia. Doctors lowered his body temperature by several degrees for two days following his injury. Now he’s slowly learning to walk again.
”I think the treatment really does work,” Gomez says.
His doctor, Dr. Steven Vanni, agrees — but adds that hypothermia is only one piece of a larger treatment puzzle. And the kind of solid research that would definitively prove whether hypothermia works for spinal cord trauma has not yet been done, Green says.
The research is further along in other fields. Two studies published in the New England Journal of Medicine in 2002 found that patients who were cooled after suffering cardiac arrest were more likely to survive and less likely to have severe brain damage than patients who were not cooled.
Both studies focused on a small sub-set of patients researchers thought most likely to benefit from hypothermia; patients had to meet several criteria, including having hearts that stopped before they were admitted to the hospital, suffering from a particular abnormal rhythm and remaining in a coma after their heartbeat had been restored by CPR.
The evidence compelled the American Heart Association to endorse the procedure last year for patients like those in the studies. Dr. Vinay Nadkarni, a University of Pennsylvania intensive care specialist who served on the committee that issued the endorsement, called hypothermia “the most promising intervention for CPR outcomes over the past 40 years.”
He cautioned, though, that more research is needed to figure out whether a broader pool of patients would benefit from hypothermia, and to determine the best methods for cooling and rewarming.
Ice Packs, Cool Air
Doctors in one of the cardiac arrest studies used ice packs; in the other they used a device that blows cool air under a blanket. In both studies it took several hours, on average, to drop body temperatures by a few degrees. Some believe they can do better by using other devices that can lower temperatures in minutes rather than hours.
At the Baptist Cardiac and Vascular Institute in Miami, Dr. Ramon Quesada will soon begin enrolling heart attack patients in a multi-center study using a device that circulates cool fluid within a closed plastic tube threaded into the patient’s veins. A study published last year showed promising results using tiny caps to cool the heads of newborns at risk for brain damage because they didn’t get enough oxygen at birth.
The original idea behind hypothermic therapy is simple: Hypothermia slows metabolism, allowing cells to survive longer when deprived of oxygen — as in the rare cases when someone falls into a frozen lake and survives after spending 20 minutes or more underwater.
Inspired by cases like these, researchers experimented with hypothermia in the 1940s and 1950s. Cooling patients became popular as a protective measure during heart and brain surgeries. But using hypothermia as therapy fell out of favor in the 1960s and 1970s with the emergence of promising new drugs and growing concerns over the risks — including potentially deadly abnormal heart rhythms — of inducing profound hypothermia.
The work of Dietrich and others in the 1980s showing the benefits of mild or moderate hypothermia — lowering body temperature by a few degrees — revived interest.
Since then, scientists have gained new insight into the way cooling reduces the problems that follow injury, such as widespread inflammation and the release of harmful chemicals that can set off a cascade of damage to surviving tissue. Hypothermia may also reduce many of the harmful chemical reactions that occur when blood flow is restored after a stroke or heart attack.
One possible problem: Mild hypothermia may inhibit the immune system and make the patient more susceptible to infection, Dietrich says. Also, it can be necessary to prescribe drugs and, in some cases, temporarily paralyze the patient to prevent shivering, which carries a low risk. A small risk is also associated with inserting a catheter to cool a patient. But in general, the risks of mild cooling appear minimal, particularly when applied in cases where the outlook is grim, doctors say.
The devil remains in the details: Which patients will benefit most? What is the best way to cool patients? How soon after injury does cooling need to begin? Should the whole body be cooled, or just one region? How cool, and for how long? And how should a patient be re-warmed?
”The great hope would be that in the near future we could appropriately identify . . . the patients at risk who could benefit, and who could be cooled quickly and safely,” said Nadkarni, reflecting on the prospects for hypothermia in cardiac arrest patients. “If we can do that, we’ve got the intervention of the century on our hands.”
By JACOB GOLDSTEIN